Wnt信号通路
生物
内胚层
细胞生物学
维甲酸
SOX2
胚胎干细胞
干细胞
前肠
细胞分化
成纤维细胞生长因子
中胚层
诱导多能干细胞
信号转导
解剖
遗传学
细胞培养
受体
基因
作者
Claudia Davenport,Ulf Diekmann,Insa Budde,Nora Tula Detering,Ortwin Naujok
出处
期刊:Stem Cells
[Wiley]
日期:2016-11-01
卷期号:34 (11): 2635-2647
被引量:44
摘要
Abstract As known from model organisms, such as frog, fish, mouse, and chicken, the anterior–posterior patterning of the definitive endoderm (DE) into distinct domains is controlled by a variety of signaling interactions between the DE and its surrounding mesoderm. This includes Wnt/FGFs and BMPs in the posterior half and all-trans-retinoic acid, TGF-β-ligands, Wnt-, and BMP-inhibitors in the anterior half of the DE sheet. However, it is currently unclear how these embryonic tissue interactions can be translated into a defined differentiation protocol for human embryonic stem cells. Activin A has been proposed to direct DE into a SOX2-positive foregut-like cell type. Due to the pleiotropic nature of SOX2 in pluripotency and developing cells of the foregut, we purified DE-cells by magnetic cell sorting and tested the effects of anteriorizing and posteriorizing factors on pure endoderm. We show in contrast to previous studies that the generation of the foregut marked by SOX2/FOXA2 double-positive cells does not depend on activin A/TGF-β-signaling but is mediated by the inhibition of Wnt- and BMP-signaling. Retinoic acid can posteriorize and at the same time dorsalize the foregut toward a PDX1-positive pancreatic duodenal cell type whereas active Wnt/beta-catenin signaling synergistically with FGF-2, BMP-4, and RA induces the formation of CDX2-positive posterior endoderm. Thus, these results provide new insights into the mechanisms behind cell specification of human DE derived from pluripotent stem cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI